Outcome and health-related quality of life in patients undergoing surgery for spinal metastases and metastatic spinal cord compression

Background Surgical treatment for spinal metastases has been shown to improve pain and neurological outcome. However, there remains limited literature on timing of surgery, effects of embolisation, prognostic scoring as well as patient-reported and health-related quality of life (HRQOL) outcome scores in this patient cohort. Furthermore, as most spinal metastases are detected at later stages, the impact of treatment on HRQOL is an important consideration in the choice of treatment. Purpose The aims of this study were to explore the importance of timing of surgery and embolisation in the neurological outcome and survival in patients undergoing urgent surgery for metastatic spinal cord compression (MSCC) [Chapters 2 and 3]; to assess the accuracy of scoring systems in predicting survival and neurological outcome in patients undergoing surgery for MSCC [Chapters 4 and 5]; to investigate the HRQOL and functional outcome following surgery for MSCC and spinal metastases [Chapter 6]; finally, to report on complications from surgical interventions in these patients as well as re-operative rates [Chapter 7]. Methods Analysis was undertaken on data, which were ambispectively-collected during the study period (retrospective 2005-2011; prospective 2011-2013). Pre-operative, intra-operative and post- operative outcome data of the functional and neurological status of all surgically treated patients for spinal metastases and MSCC including HRQOL scores, complications and survival were analysed. Results This thesis found earlier decompression surgery (within 24 hours of acute presentation) in patients with MSCC (n=121; mean age 61 years (17-86); 75M: 46F), resulted in a better neurological improvement compared to surgery after 24 hours (p = 0.01). However, the post- operative length of hospital stay, complications or patient survival were not influenced by earlier surgical intervention [Chapter 2]. With regard to embolisation and surgery for vascular renal cell metastases to the spine (n = 25), it was shown that blood loss (just over a mean of 1.5l) and complications (in 1/3 of patients) remained concerning; the timing and grade of embolisation did not significantly affect intra-operative blood loss [Chapter 3]. Linear regression modelling showed that more extensive cord compression by metastases, as given by the Epidural Spinal Cord Compression Scale (ESCC) scale, led to significantly greater blood loss, and that it was still important to perform spinal surgery even in higher grades of cord compression to improve neurological outcome [Chapter 4]. Focus then turned to the popular prognostic scoring system for survival - the revised Tokuhashi score. In a large study of over 200 patients, there appeared to be only a modest agreement of 66% between the predicted (from the revised Tokuhashi score) and the actual survival [Chapter 5]. A detailed prospective analysis of patient-reported outcome and quality of life scores in 199 patients undergoing surgery for spinal metastases showed that surgical treatment did significantly improve pain and HRQOL [Chapter 6]; the overall complication rate was 27%. In the penultimate chapter [Chapter 7], a modest re-operation rate (10%) is reported in patients treated surgically for spinal metastases, and most of these re-operations were for surgical site infection and were performed during the same admission as the primary surgery. The survival times did not differ significantly in those patients who received single surgery against those patients who underwent revision surgery (single surgery n = 258, median survival 250 days (5-2597) vs. revision n = 31, median survival 215 days (9-1352); p = 0.722). Conclusions In conclusion, this thesis has found that earlier surgery for MSCC is associated with improved neurological outcome. Timing or the grade of pre-operative embolisation did not significantly affect intra-operative blood loss in surgery for vascular renal cell spinal metastases, suggesting that other factors could play a role. Indeed, a linear regression model did reveal significantly greater blood loss to be associated with a higher degree of MSCC (as given by the ESCC scale), and that decompression surgery was still beneficial even with the more severe grades of cord compression. The revised Tokuhashi scoring system showed only modest agreement for survival suggesting that some of the parameters within this scoring system remained important and need further investigation. Very convincing evidence was provided from patient-reported outcomes and quality of life scores that surgical treatment did significantly improve pain and health-related quality of life in these patients. Finally, one in four patients sustained a complication and there was a 10% re-operation rate in a large cohort of surgically treated patients for spinal metastases, where most of these re-operations were for surgical site infection performed during the same admission as the primary surgery. It was beneficial for these patients to undergo revision surgery to achieve comparable survival (to those not having revision surgery)

CFD Investigation of Empty Flanged Diffuser Augmented Wind Turbine

Enclosing a wind turbine within a Flanged diffuser is an innovative mean to increase the power harvested by turbine blades and it is among the most effective devices for increasing wind turbine energy. The geometric parameters of the empty flanged diffuser contribute efficiently to increase mass flow in the diffuser, hence improve the turbine performance. The study presents developed models of the geometrical parameters of an empty flanged diffuser that suitable for a scaled-down (1-6.5) horizontal axis wind turbine, the geometry parameters were involved the diffuser length, diffuser angle, flange height and flange angle. The geometrical models were verified and CFD investigated in 2-D and 3-D domains. Results obtained from CFD simulations show that when using a compact size of flanged diffuser within optimum geometrical parameters can give well acceptable for flow velocity increase at suggested place for the turbine rotor install where the increase in flow velocity is due to lower pressure at the outlet of the diffuser. As there is also a significant effect of the flange angle on increasing the flow velocity inside the diffuser where the rate of increase in wind velocity at turbine position was calculated for two flange angles (0 ÌŠ and 5 ÌŠ ) . In another hand, the results also provided information on the velocity contours and velocity streamlines around diffuser geometry

Prospective analysis of health-related quality of life after surgery for spinal metastases

Purpose Most spinal metastases are detected late and thus the impact of treatment on the health related quality of life (HRQOL) is an important consideration. This study investigated the HRQOL following surgery for spinal metastases. Methods Prospective study of patients operated for symptomatic spinal metastases, at a single tertiary referral spine centre (2011-2013). Data was collected pre-operatively and up to 2 years following surgery (if alive). The HRQOL assessment was performed using recognised systems including the Frankel Score (neurological status), EQ-5D and the Oswestry Disability Index. Results 199 patients were studied (median age 65yrs, 43% (86) F; 57% (113) M). The Frankel score improved significantly after surgery in 69 patients (35%), worsened in 17 (8%), with 20/39 patients regaining the ability to walk (51%). All the HRQOL scores improved significantly following surgery. The complication rate was 27%; median survival 270 days, and 44 patients (22%) survived at 2 years. Conclusions This large prospective study showed that surgical treatment for spinal metastases significantly improved the HRQOL

ASSERT (Acute Sacral inSufficiEncy fractuRe augmenTation): randomised controlled, feasibility trial in older people

Objective To determine the feasibility of designing and conducting a definitive trial to evaluate the effectiveness of sacral fracture fixation compared with non-surgical management among older people admitted with a lateral compression pelvic fragility fracture (PFF). Design Single-site, parallel, two-arm randomised controlled feasibility trial. Setting A UK tertiary centre hospital. Participants Patients aged ≥70 years who were ambulating pre-injury requiring hospital admission (within 28 days of injury) with a type 1 lateral compression PFF. Interventions The intervention group received sacral fracture fixation (cement augmentation±screw fixation) within 7 days of randomisation. Routine preoperative and postoperative care followed each surgical intervention. The control group received usual care consisting of analgesia, and regular input from the medical and therapy team. Primary and secondary outcome measures The feasibility outcomes were the number of eligible patients, willingness to be randomised, adherence to allocated treatment, retention, data on the completeness and variability of the proposed definitive trial outcome measures, and reported adverse events. Results 241 patients were screened. 13 (5.4%) were deemed eligible to participate. Among the eligible participants, nine (69.2%) were willing to participate. Five participants were randomised to the intervention group and four to the control group. The clinicians involved were willing to allow their patients to be randomised and adhere to the allocated treatment. One participant in the intervention group and two participants in the control group received their allocated treatment. All participants were followed up until 12 weeks post-randomisation, and had an additional safety follow-up assessment at 12 months. Overall, the proportion of completeness of outcome measures was at least 75%. No adverse events were directly related to the trial. Conclusions There were significant challenges in recruiting sufficient participants which will need to be addressed prior to a definitive trial. Trial registration number ISRCTN16719542

The Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments

Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale.

INTRODUCTION: Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh. METHODS AND ANALYSIS: The study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants' source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants. ETHICS AND DISSEMINATION: The study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02746003; Pre-results

Advancing the Understanding of Clinical Sepsis Using Gene Expression-Driven Machine Learning to Improve Patient Outcomes

Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of Machine Learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. ML has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management

A Transcriptomic Appreciation of Childhood Meningococcal and Polymicrobial Sepsis from a Pro-Inflammatory and Trajectorial Perspective, a Role for Vascular Endothelial Growth Factor A and B Modulation?

This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)–VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis